Altered Ecology of the Respiratory Tract Microbiome and Nosocomial Pneumonia

Abstract

Nosocomial pneumonia is one of the most frequent infections in critical patients. It is primarily associated with mechanical ventilation leading to severe illness, high mortality, and prolonged hospitalization. The risk of mortality has increased over time due to the rise in multidrug-resistant (MDR) bacterial infections, which represent a global public health threat. Respiratory tract microbiome (RTM) research is growing, and recent studies suggest that a healthy RTM positively stimulates the immune system and, like the gut microbiome, can protect against pathogen infection through colonization resistance (CR). Physiological conditions of critical patients and interventions as antibiotics administration and mechanical ventilation dramatically alter the RTM, leading to dysbiosis. The dysbiosis of the RTM of ICU patients favors the colonization by opportunistic and resistant pathogens that can be part of the microbiota or acquired from the hospital environments (biotic or built ones). Despite recent evidence demonstrating the significance of RTM in nosocomial infections, most of the host-RTM interactions remain unknown. In this context, we present our perspective regarding research in RTM altered ecology in the clinical environment, particularly as a risk for acquisition of nosocomial pneumonia. We also reflect on the gaps in the field and suggest future research directions. Moreover, expected microbiome-based interventions together with the tools to study the RTM highlighting the “omics” approaches are discussed.

Developmental progression of the nasopharyngeal microbiome during childhood and association with the lower airway microbiome

“…We also employed decontam to identify and remove likely contaminant sequences by comparing our samples against negative controls. 30 While these methods are not guaranteed to completely resolve the challenges of low abundance sequences, we are encouraged by the findings in our data that match and support previous literature and our understanding of airway microbial ecology.…”

Intrapulmonary Treatment With a Novel Tlr4 Agonist Confers Protection Against Klebsiella Pneumonia

“…Prolonged intubation predisposes patients to ventilator-associated pneumonia (VAP) by introducing a foreign body into the airway and changing the respiratory tract microbiome via frequent suctioning, chronic aspiration, and antibiotic exposure (23). Evidence indicates that alterations in the respiratory microbiome facilitate pulmonary dysbiosis, altered immune function, and an increased burden of nosocomial pathogens (3,24). Novel treatments that have been proposed to protect intubated patients from VAP include probiotics to restore the respiratory tract microbiome and bacteriophage-based therapies (25,26).…”

“…Hospital-acquired infections contribute significantly to increased morbidity and mortality in hospitalized patients and generate a significant economic burden on health care systems in the United States (1). Critically ill, surgical, and elderly patients are vulnerable to nosocomial pneumonia (1)(2)(3). Furthermore, an increase in antibiotic resistance among hospital-acquired pathogens is a rising global threat (4,5).…”

Further Quantifying the Niche-Neutral Continuum of Human Digestive Tract Microbiomes with Near Neutral Model and Stochasticity Analysis

“…Strictly speaking, DT should be considered as the tract where solid and liquid food are in touch with human mucosa to be processed as nutrients, and overlapping respiratory tract is the tract where inhaled air is in touch with human mucosa. 33 Furthermore, the delineation of 4 2 or proposed 5 niches may simply be the “checkpoints” on the niche-neutral continuum, likely influenced by the sampling scheme adopted by Segata et al 2 A second limitation of this study is to do with the computational nature of this study, which depends on statistical inferences and simulations to infer ecological insights from species abundance distributions (SAD) in the human DT microbiome. The SAD data were from sequencing microbiome samples, and no manipulative experiments (which are generally infeasible for healthy humans for ethic reasons) data are available.…”